Baker Institute Annual Report 2017https://bakercornell.org
Baker Institute Annual Report 2017Fri, 08 Dec 2017 15:54:53 +0000en-UShourly1https://wordpress.org/?v=4.9.1https://bakercornell.org/wp-content/uploads/sites/3/2017/10/favicon-150x150.pngBaker Institute Annual Report 2017https://bakercornell.org
3232Can we develop broad-spectrum antiviral drugs to treat multiple viral infections?https://bakercornell.org/can-we-develop-broad-spectrum-antiviral-drugs-to-treat-multiple-viral-infections/
Thu, 26 Oct 2017 20:39:35 +0000https://bakercornellarchives.org/2017/?p=115A host of viruses have evolved ingenious ways to cause disease in humans and animals. We have vaccines to prevent viral infections, but only for a few selected viruses. Although antiviral drugs exist, they treat an even smaller number of viral infections. Each of these antiviral drugs targets just a single virus, resulting in the need for a new drug for every virus. New viruses are constantly infecting animals and humans, requiring frequent development of new drugs. Other viruses only infect very few people or animals, resulting in limited commercial interest in developing drugs against them.

On the other hand, each bacteria-killing antibiotic is effective against many different bacteria. As a result, we always have an antibiotic available to treat even new or rare bacterial infections. It would be ideal to also have broad-spectrum antiviral drugs that work against as many viruses as possible. Researchers in Schang’s group are looking for common strategies used by unrelated viruses to enter cells and reproduce. This approach is well-suited to identify viral Achilles’ heels to aid in the development of broad-spectrum antiviral drugs.

Most viruses have a coat of oily lipid molecules called an envelope, which is very similar to a cell membrane. The virus envelope must fuse with the cell membrane to dump the viral contents into the cell. Schang and his group have identified molecules that block this fusion, preventing viral entry and its consequent replication. These molecules are active against a number of viruses that infect humans and companion animals.

A related project also aims to keep viruses out, by preventing them from latching onto sugar molecules on the cell surface. Most viruses latch to one of two different types of sugars, but Schang’s group has discovered a family of molecules that blocks latching to both, thus preventing infection by a number of viruses that infect companion animals and humans.

Schang and his group are finding common principles among many different viral infections, while also bringing to light novel molecules that can be further tailored toward life-saving antiviral drugs. The most advanced of Dr. Schang’s molecules has been optioned by a startup, which is exploring its clinical potential.

Treatments using stem cells, which can replenish tissues with new cells, offer tremendous potential for healing wounds and treating various diseases, but we need to learn much more about these cells before this potential can be realized.

Van de Walle’s research on adult stem cells spans multiple veterinary species to understand the roles of these cells in healing and cancer formation. Members of her lab are looking at how equine mesenchymal stem cells, stem cells collected from horse blood, encourage wound healing and protect against bacterial and viral infections in horses. They also study how epithelial stem cells, the cells that are thought to originate several cancers, are regulated in the mammary gland of horses. These studies are aimed at understanding why horses rarely develop breast cancer, a cancer that is so common in humans, cats, and dogs.

A better understanding of both the benefits and limits of stem cell treatments is required before stem cells can be used to develop safer, more targeted therapies. Through this comparative approach using multiple species, Van de Walle’s work is also finding differences in mammary stem cells in species that are more or less prone to suffer from breast cancer, looking for clues to how breast cancer can develop.

]]>How can we improve environmental sustainability and public health through reproductive technologies?https://bakercornell.org/how-can-we-improve-environmental-sustainability-and-public-health-through-reproductive-technologies/
Thu, 26 Oct 2017 20:33:58 +0000https://bakercornellarchives.org/2017/?p=109A keen understanding of reproduction is vital to helping endangered species, domestic dogs, and people. Travis first became interested in research to obtain this understanding with the goal of eventually being able to manage zoo and wildlife populations with effective contraceptives and by enhancing their fertility. The reproductive technologies resulting from such approaches can also be leveraged to improve human health.

As an example, his investigations into sperm structure and function resulted in scientific discoveries that led to the development of a diagnostic test currently used in human fertility clinics to determine sperm quality, thereby helping clinicians counsel patients about optimal treatment using assisted reproduction. His idea to copy a design from the sperm tail led to a method for attaching enzymes to microscopic, nano-sized, particles. Travis is now looking for ways to apply these “tethered enzymes” in the diagnosis of diseases and to power implantable medical devices.

His work on assisted reproduction included performing the first successful in vitro fertilization in dogs in 2015. Travis’ group is now advancing that work to develop gene repair technologies. Such technologies are critical to correcting genetic diseases without losing genetic diversity in domestic dogs. They could also be applied to the preservation of endangered species, such as the red wolf or the African painted dog.

]]>Why do different animals get different kinds of allergies?https://bakercornell.org/why-do-different-animals-get-different-kinds-of-allergies/
Thu, 26 Oct 2017 20:30:18 +0000https://bakercornellarchives.org/2017/?p=107The same skin allergies and rashes make dogs and humans itch, but dogs don’t often develop lung allergies like humans. Allergies in all species occur when the immune system, which normally fights infections, mistakenly attacks a harmless allergen like pollen. However, we don’t understand why some species are more prone to certain allergic diseases and how the immune system can work for an animal during infection, and against it during allergy.

To answer these questions, Tait Wojno studies parasitic worm infections and allergies in multiple species. She and her team investigate how dog, mouse, and human immune systems function to create good responses that control infections or bad responses that lead to allergies. Specifically, they are looking at how rare types of white blood cells called basophils and innate lymphoid cells contribute to immune responses during worm infections and allergies.

Through this work, Tait Wojno hopes to fill a major gap in our understanding of why different species suffer from different types of allergies. This research may also help to reveal how the immune system can have both good and bad effects in all species.

]]>How a virus affecting birds 7,000 miles away created problems for our dogshttps://bakercornell.org/how-a-virus-affecting-birds-7000-miles-away-created-problems-for-our-dogs/
Thu, 26 Oct 2017 20:27:59 +0000https://bakercornellarchives.org/2017/?p=105A virus that was identified as the H3N2 strain of influenza, first seen in the Chicago area in early 2015, underwent a resurgence in the United States this year. Infected dogs experience a respiratory disease which lasts for a few days, accompanied by a fever and cough as seen with influenza in humans, and are infectious to other dogs for about a week.

One focus of the Parrish laboratory is to study how viruses emerge and spread among animals and humans, and then use that information to identify new ways to control them. Parrish and his group figured out that the new flu virus had originally jumped from birds to dogs in Asia circa 2005 and that the strain in Chicago came from Korea, where it had been circulating in dogs for several years.

A new outbreak of canine influenza was reported in Los Angeles earlier this year. Parrish and his group were able to use the methods they have developed to examine the genetic fingerprint of this virus and identify it as an H3N2 variety. However, they discovered that it was a different strain than the one that originated in southern China, and was probably brought to the United States by dogs that were rescued from dog markets. The infected dogs were quarantined until they were no longer contagious, thus preventing the spread of a new strain of influenza virus in the United States.

]]>How do viruses trick cells into creating viral “factories”?https://bakercornell.org/how-do-viruses-trick-cells-into-creating-viral-factories/
Thu, 26 Oct 2017 20:24:00 +0000https://bakercornellarchives.org/2017/?p=102Although they are not often heard of, reoviruses cause disease in multiple animal hosts. Rotaviruses, for example, commonly cause diarrhea in young children, a disease which is often deadly in developing countries. Unfortunately, there are no antivirals that are effective against reoviruses.

When a cell detects a viral infection, its first response is to shut down its protein-making machinery so that the virus can’t use it to reproduce itself. Researchers in the Parker lab work with reoviruses that infect mammals, viruses which have evolved an ingenious way of overcoming this cellular response. Reoviruses form viral “factories” inside cells. They make a gooey compartment that sequesters away the cellular protein-making machinery, effectively allowing the virus to corner the market on protein production. Recently, the Parker group identified the two viral proteins that form these blob-like factories.

Parker’s work illuminates this poorly understood viral strategy. The more we learn about these viruses, the more likely we are to eventually cure these serious viral infections in humans and animals.

]]>How can we diagnose and eradicate reproductive disorders in dogs?https://bakercornell.org/how-can-we-diagnose-and-eradicate-reproductive-disorders-in-dogs/
Thu, 26 Oct 2017 20:21:51 +0000https://bakercornellarchives.org/2017/?p=100Many dog breeds are susceptible to inherited disorders of sexual development, or DSDs. One such disorder, XX DSD, can lead to mismatched reproductive organs, sterility, tumors, and infections. XX DSD is a bane to breeders, but so far has been impossible to remove from the gene pool.

Meyers-Wallen’s group is working to pinpoint the cause of XX DSD and to understand how the disorder is inherited. By working with a family of dogs that carries the disorder and performing DNA sequencing and genetic screens, they have narrowed down the location of the relevant area on the dog genome connected to the problem. Her work has demonstrated that the inheritance of the disorder is not straightforward and she suspects that epigenetic factors, which are inherited changes that regulate gene expression, may also play a role.

Meyers-Wallen’s research has yielded a clearer understanding of the genetic cause of XX DSD. This knowledge is necessary for the development of any diagnostic test that could be used to ultimately eradicate this harmful disorder in purebred dogs.

Humans and animals have nearly 20,000 different genes which encode the myriad of proteins that affect all aspects of an individual – the way individual cells work, our organs, even influencing how we think and behave. Other animals have basically the same 20,000 genes – so why are you a human and your dog isn’t?

The smallest difference in expression of any of those genes and proteins affects everything from an individual’s health to the subtle differences that make animals or people differ from each other, or the bigger differences between species. Danko and his group have developed a technique called ChRO-seq, which allows them to look at the subtle differences in gene expression in cells under different conditions. ChRO-seq tags RNA polymerase, the enzyme in cells that converts the DNA encoding our genes into RNA, allowing scientists to see which genes are being used by the cell. It also defines the location of control switches in our genomes, called “enhancers”, that control which parts of our body use which genes.

By understanding the detailed patterns of expression of all genes, the Danko laboratory is decoding the rules that underlie our health and well-being. This information also helps us to understand what happens when disease occurs, whether it be cancer or one of the many other diseases that arise when gene regulation is altered, causing the usually well-functioning gene orchestra to play out of tune.

]]>How can we better treat breast cancer in people and hemangiosarcoma in dogs?https://bakercornell.org/research-update-how-can-we-better-treat-breast-cancer-in-people-and-hemangiosarcoma-in-dogs/
Thu, 26 Oct 2017 19:51:16 +0000https://bakercornellarchives.org/2017/?p=95Cancers are major diseases in humans and dogs. In humans, a drug that many survivors of breast cancer take to prevent a relapse, called tamoxifen, often stops working after several years of treatment. Unfortunately, it is still unknown why it stops working, and there is currently no way to predict which patients may or may not stop responding to it. In dogs, an aggressive tumor in the blood vessels, called hemangiosarcoma, kills up to 2 million dogs yearly, yet effective treatments do not exist. Most unfortunately, the extremely limited knowledge available about these dog tumors, which are unlike any prominent human cancer, is a major roadblock to the development of effective therapies.

Regarding human cancers, researchers in the Coonrod lab are working on finding cellular pathways that enable breast cancer cells to become resistant to tamoxifen. Finding these pathways is critical if we are ever going to discover new ways to prevent or block the tumor’s resistance to this type of therapy.

With respect to dog tumors, Coonrod’s group is applying the most advanced techniques in human cancer research to identify any particular genes, or groups of genes, that may drive the tumor’s growth. Pinpointing these genes is only a first step, but a significant one in deciding how to best develop effective therapeutics against these tumors.

When a mammal becomes pregnant, the mother’s immune system is prevented from attacking the fetus as if it were an unfamiliar infection, but the mechanisms for this state of tolerance are not well understood. The Equine Genetics Center at the Baker Institute has pioneered methods to study the horse placenta and to determine the role of the placenta in protecting the fetus from immune destruction by the mother. The group has developed a novel experimental system of trophoblast transplantation that has demonstrated that the placenta acts to affect its own survival independently of the hormonal state of pregnancy and, most recently, that it can survive not only primary immune responses, but also the stronger secondary responses of the type that occur after vaccinations.

The Antczak lab’s work on the equine placenta contributes to knowledge of reproduction and pregnancy loss in horses, and in humans, too. It also has relevance to the important question of why the immune system can tolerate the unfamiliar tissues of the fetus, but not a foreign organ transplant. Without this type of new information, we are unlikely to ever be able to replace the immunosuppressive treatment of transplant patients with other approaches that do not increase their vulnerability to infectious diseases.